Colletofragarone A2 and Colletoins A-C from a Fungus Colletotrichum sp. Decrease Mutant p53 Levels in Cells.

p53 is frequently mutated in tumor cells. Mutant p53 (mut p53) accumulates in cells to promote cancer progression, invasion, and metastasis, and it is attracting attention as a target for cancer therapies. In this study, we used immunofluorescence staining of Saos-2 cells harboring doxycycline-inducible p53R175H [Saos-2 (p53R175H) cells] to search for compounds from natural sources that can target mut p53 and found an extract of Colletotrichum sp. (13S020) that was active. Bioassay-guided fractionation of the extract afforded a known polyketide, colletofragarone A2 (1), and three new analogues, colletoins A-C (2-4). The relative and absolute configurations of 1 were determined by the spectroscopic method and DFT calculation. Compounds 1 and 2 inhibited the growth of Saos-2 (p53R175H) cells and decreased mut p53 in the cells.